1. Field of the Invention
The present invention relates in a broad aspect to methods and compositions for the rejuvenation of human skin, treatment of skin disorders and for the general improvement in the quality and appearance of the skin. More particularly, the present invention is directed to treatment methodologies utilizing topically applied vitamin A propionate compositions to effectively retard and reverse the effects of photoaging of the skin and environmental damage and to treat acne without the unpleasant side effects associated with known vitamin A skin treatments. Other dermatological conditions effectively treated through the present invention include those linked to disorders of keratinization such as ichthyosis (hyperkeratosis), Darier's disease, acne, psoriasis and similar conditions. Also, vitamin A propionate is effective for treatment of early skin degeneration such as actinic keratosis, lentigos and melasma.
2. Description of the Prior Art
It is known that excessive sun exposure and general exposure to the environment causes anatomic degradation of human skin which is cumulative over time. The symptoms of such degradation are most pronounced on the face and around the eyes and are commonly manifested as wrinkles, blotchy discolorations, leathery skin texture, dryness, roughness, and premalignant growths. These symptoms are particularly apparent in light-skinned people who sunburn easily and in the elderly. Though skin has a natural ability to repair such damage, with aging the ability of the skin to spontaneously repair itself decreases. In addition, because the degradative effects of environmental exposure are cumulative over time, adults who have had excessive sun or environmental exposure in childhood may develop serious dermal alterations. Typically, such alterations remain microscopic long before the gross products of skin degradation noted above become visible. Then, in early adulthood, the degradation effects associated with such microscopic alterations are manifested as early aging of the skin.
Early efforts at treating human skin utilized vitamin A as a therapeutic agent. Vitamin A has been known since the 1940s to be an essential vitamin for the nutritional health of the skin. Early research showed the ability of vitamin A to stimulate new cell growth in the epithelium and to produce a softer and smoother skin appearance. In order to achieve these results, early skin treatment methodologies administered vitamin A internally, in large doses, usually in the form of the ester of palmitic acid, known as vitamin A palmitate. However, these vitamin A derivative treatments frequently resulted in hypervitaminosis-A toxic symptoms with such undesirable side effects as hair loss, migraine headaches, fatigue, and bone pain.
The beneficial effects of vitamin A in its acid form (retinoic acid) as a topical therapeutic agent are also well known in the art of dermatology. U.S. Pat. No. 3,729,568 discloses the repeated topical application of vitamin A acid to areas of the skin to clear the symptoms of acne. U.S. Pat. No. 4,603,146 discloses the beneficial effects of low strength applications of vitamin A acid in reportedly retarding the effects of aging on the skin. Such use of vitamin A acid in a maintenance therapy program reportedly results in a lightened skin, diminished wrinkling, and the disappearance of early sun-damaged spots such as actinic keratoses. Treatment with sufficient quantities of retinoic acid for therapeutic results, however, is known to cause visible irritation and inflammation of the skin. As a result, the skin exhibits an abnormal redness, or erythema, often followed by painful and unpleasant peeling of the skin which can be severe. Because these side effects are frequently difficult to tolerate by patients who otherwise would benefit from its use, retinoic acid as a skin treatment has limited applicability and must be carefully monitored. It must be dispersed with a physician's prescription.
It is known that vitamin A acid induces self-proliferation and new cell growth. Its effectiveness in the treatment of acne is related to this increase in the skin's regenerative capacity. Normally the turnover the skin takes 28 days for a new cell to form and shed off to the environment. Vitamin A acid reduces this regeneration time to between 10 and 15 days. As a result, the thickness of the uppermost layer of the skin, the epidermis, is doubled. The skin cell layer on the surface (stratum corneum) is reduced from 14 cell layers of impacted cells to eight or nine layers of loosely woven skin cells. There is also evidence that deeper down in the skin in the dermis there is new collagen formation as well as new blood vessel formation. The end result of this rapid regeneration is the peeling off of sun-damaged spots and an exfoliation of impactions of acne. There is also a gradual reduction in the fine lines and wrinkles.
Unfortunately, as noted above, a particular disadvantage of the topical use of vitamin A acid preparations is the high level of skin irritancy which follows their application. The abrasive effect of the use of such compositions often causes undesirable peeling of the skin surface epithelium and an accompanying surface roughness along with abnormal redness. Such contraindications are not only cosmetically undesirable but painfully uncomfortable for the patient. In addition, such vitamin A acid preparations are most effectively applied using an alcohol solvent system which causes its own uncomfortable burning sensation. This discomfort is particularly amplified when used on skin which has been peeled from previous uses of vitamin A acid.
Early attempts at avoiding the burning sensations caused by the use of alcohol carrier vehicles utilized preparations of vitamin A acid in cream vehicles. However, such creams were shown to be of limited usefulness, apparently because the cream binds a significant portion of the vitamin A acid, resulting in a system with diminished activity. Additionally, emulsifiers which are formulated into the creams frequently contribute to acne formation.
Other attempts at overcoming the undesirable side effects of vitamin A acid treatment utilized derivatives of vitamin A such as the various fluorinated forms of the acid as well as the limited number of the acid's amides and esters disclosed in U.S. Pat. Nos. 4,654,354, 4,395,575, 4,335,248, 4,304,787, 4,299,995, 4,231,944, 4,21 6,312, 4,214,000, 4,194,007, 4,171,318, 4,129,662, 4,126,699, 4,126,698, 4,126,697, 4,126,693, 4,055, 659 and 3,984,544. Surprisingly, only a few of the many amides and esters of vitamin A acid disclosed showed any promise as agents for the treatment of skin disorders. Moreover, none were completely effective at eliminating the undesirable side effects of vitamin A treatment.
Accordingly, it is a principal object of the present invention to provide an improved methodology and associated pharmaceutical composition for therapeutically retarding and reversing the effects of skin photoaging and for the treatment of acne and other dermatological disorders without the abrasive and irritating characteristics of known treatments. It is a further object of the present invention to provide an effective skin treating composition which avoids the use of alcohol as a delivery solvent while maintaining its activity as a pharmaceutical preparation. It is an additional object of the present invention to provide a skin treatment methodology that accounts for variations in skin type so that a skin care regimen can be effectively maintained.